Smoldering Multiple Myeloma Research Promising but Not Yet Translatable to Change in Care

As investigators have learned more about how to diagnose and categorize smoldering multiple myeloma (SMM), a new review article argues there’s insufficient data to evolve beyond a close observation approach.

Emerging therapies are raising hopes that clinicians can take a more proactive approach to caring for patients with high-risk smoldering multiple myeloma (SMM), but a new review article suggests there is still insufficient evidence to rewrite the standard of care.

Writing in the journal Cancers, corresponding author Noopur Raje, MD, of Massachusetts General Hospital and Harvard Medical School, and colleagues review changes in the definition and risk stratification of SMM and look at efforts to slow or prevent progression to active MM. At present, the authors note, the strategy upon diagnosis is typically a “wait-and-see” approach. However, the day may be near when clinicians can move beyond close observation and instead offer intervention.

“[T]here have been significant efforts to refine the diagnosis of SMM,” they write. “Moreover, the increasing recognition of patient subsets with a high risk for progression and the availability of more effective and better tolerated drugs for MM have motivated investigations into early intervention to delay or arrest progression to symptomatic disease.”

One change in treating SMM has been defining and categorizing it. In 2014, the International Myeloma Working Group (IMWG) revised its definition of MM such that 10-15% of patients were up-staged, including the redefinition of patients with SMM and an 80% or higher risk of progression within 2 years. Under the new guidelines, those patients are now considered to have active disease requiring treatment.

The working group suggests low-dose whole-body CT scans as the primary initial method of detecting lytic lesions. If the results are negative or inconclusive, whole-body MRIs are indicated.

Among patients diagnosed with SMM, Raje and colleagues note that the risk of progression will vary significantly from patient to patient. Newer strategies for categorizing risk include biomarkers associated with increased tumor burden. For instance, the authors note that patients with immunoglobulin A monoclonal protein SMM face shorter times to progression (TTP) compared to patients with other types of SMM. Immune signature profiles also appear to be important to understanding a patient’s unique risk of progression, they write. These findings and others have helped investigators develop more refined models for calculating risk.

Still, Raje and colleagues note that it’s still difficult to know which precise patients will require early intervention, and how best to treat those who do.

Given the limitations of existing research, the authors suggest the close observation approach remains the best approach once a patient is diagnosed with SMM.

The IMWG recommends follow-up 3 months after diagnosis, followed by check-ups every 4 to 6 months during the first year, and every 6 to 12 months after that, along with annual imaging.

As for the question of intervention, Raje and colleagues note that a number of studies recently have begun to investigate the role of early intervention in SMM.

“Results from these studies and mature data on [overall survival] will provide further guidance in the broad incorporation of early intervention as standard practice in high-risk SMM in order to delay or prevent progression,” they write.

For now, though, high-risk patients ought to be monitored very closely and, when possible, enrolled in clinical trials that will help the scientific community better understand the potential of intervention.


Kim EB, Yee AJ, Raje N. Treatment of smoldering multiple myeloma: Ready for prime time? Cancers. 2020;12(5):1223. doi:10.3390/cancers12051223

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